Saul Roseman (1921—2011)

BY Ronald L. Schnaar AND George W. Jourdian

Saul Roseman, professor emeritus of biology at The Johns Hopkins University, died peacefully July 2 after a career in science of nearly 70 years. He had profound effects on the field of glycobiology and on our understanding of bacterial sugar transport. His scientific enthusiasm and intensity were prodigious and contagious. He leaves a distinguished legacy of discovery.

Roseman attended City College of New York, where he obtained a Bachelor of Science in 1941. He earned his Ph.D. in 1948 under the mentorship of Karl Link at the University of Wisconsin. His doctoral pursuit included a hiatus to serve as an infantryman in World War II. During his postdoctoral studies at the University of Chicago with Albert Dorfman, he studied glycosaminoglycans, initiating a lifelong interest in hexosamine metabolism. In 1953, he joined the Rackham Arthritis Research Unit at the University of Michigan Medical School as an assistant professor.

At Michigan, his research initially concentrated on the metabolism of sialic acids, prominent cell-surface determinants and among the most abundant sugars that terminate the oligosaccharide chains of glycoproteins and glycolipids. Within a short time, he and postdoctoral researcher Don Comb convincingly proved that sialic acid contained N-acetylmannosamine, an unexpected finding because numerous investigators had concluded that the hexosamine constituent of sialic acid was N-acetylglucosamine. Roseman’s manuscripts reporting the correct structure of sialic acid were clear, rigorous, thorough and compelling, a style of research and communication that remained a hallmark throughout Roseman’s career.

The finding initiated a remarkably productive period of seminal findings in the Roseman laboratory, including the discovery of pathways for the biosynthesis and degradation of sialic acids, isolation and characterization of CMP-sialic acid, and demonstration of its role as the nucleotide sugar donor for the biosynthesis of sialylated glycans, enzymatic pathways for hexosamine biosynthesis, and characterization of glycosyltransferase activities in tissues and bodily fluids.

During a summer stint in H. Gobind Khorana’s laboratory, Roseman devised a chemical means to synthesize sugar nucleotides. The availability of these compounds in large amounts cleared a path for investigators to study the biosynthesis of the oligosaccharide chains of glycoproteins and glycolipids.

Roseman and his team were exploring the metabolism of N-acetylmannosamine by bacteria when they stumbled upon a finding that provided new insights into bacterial sugar transport. As one of the controls for ATP-dependent hexosamine phosphorylation by Escherichia coli, phosphoenolpyruvate was added. Surprisingly, bacteria failed to transfer phosphate from ATP to ManNAc but robustly transferred phosphate from phosphoenolpyruvate. Eventually, the Roseman team purified and characterized the bacterial phosphotransferase systems that simultaneously transport and phosphorylate sugars. The biochemistry, thermodynamics and function of the PTS were explored vigorously by Roseman and his collaborators.

Later in his career, Roseman focused on the roles of glycans in cell-cell recognition and on chitin metabolism by Vibrio and other bacteria. At the time of his death, his laboratory at Johns Hopkins continued to pursue these goals, and Roseman hoped to make substantial contributions well into his 10th decade. He never lost his enthusiasm and passion for the next experiment.

Roseman’s seminal discoveries often were characterized as serendipitous, because both the correct structure of sialic acid and the PTS system were unexpected findings. Of this, Roseman once said, “The unexpected is just nature’s way of telling researchers where to look for the really interesting and important stuff.” Interesting, indeed!

Roseman was recognized widely as a pioneer in biochemistry and glycobiology, was inducted into the National Academy of Sciences, and received the Gairdner Foundation International Award, the Rosenstiehl Award and an honorary M.D. from the University of Lund in Sweden. The Journal of Biological Chemistry honored him with a centennial biography, “Hexosamine metabolism, sialic acids, and the phosphotransferase system: Saul Roseman’s contributions to glycobiology.” His insights, passion and enthusiasm for research live on in the many scientists who trained with him or benefited from his work.

Ronald L. Schnaar (schnaar@jhu.edu) is a professor in the department of pharmacology at The Johns Hopkins School of Medicine, and George W. Jourdian (gjourdia@med.umich.edu) is a professor emeritus of biological chemistry and internal medicine at the University of Michigan Medical School.